Document Detail


Tempol prevents altered K(+) channel regulation of afferent arteriolar tone in diabetic rat kidney.
MedLine Citation:
PMID:  22252401     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Experiments were performed to test the hypothesis that oxidative stress underlies the enhanced tonic dilator impact of inward-rectifier K(+) channels on renal afferent arterioles of rats with streptozotocin-induced diabetes mellitus. Sham and diabetic rats were left untreated or provided Tempol in their drinking water for 26±1 days, after which afferent arteriolar lumen diameter and its responsiveness to K(+) channel blockade were measured using the in vitro blood-perfused juxtamedullary nephron technique. Afferent diameter averaged 19.4±0.8 μm in sham rats and 24.4±0.8 μm in diabetic rats (P<0.05). The decrease in diameter evoked by Ba(2+) (inward-rectifier K(+) channel blocker) was 3 times greater in diabetic rats than in sham rats. Glibenclamide (K(ATP) channel blocker) and tertiapin-Q (Kir1.1/Kir3.x channel blocker) decreased afferent diameter in diabetic rats but had no effect on arterioles from sham rats. Chronic Tempol treatment prevented diabetes mellitus-induced increases in both renal vascular dihydroethidium staining and baseline afferent arteriolar diameter. Moreover, Tempol prevented the exaggeration of afferent arteriolar responses to Ba(2+), tertiapin-Q, and glibenclamide otherwise evident in diabetic rats. Preglomerular microvascular smooth muscle cells expressed mRNA encoding Kir1.1, Kir2.1, and Kir6.1. Neither diabetes mellitus nor Tempol altered Kir1.1, Kir2.1, Kir6.1, or SUR2B protein levels in renal cortical microvessels. To the extent that the effects of Tempol reflect its antioxidant actions, our observations indicate that oxidative stress contributes to the exaggerated impact of Kir1.1, Kir2.1, and K(ATP) channels on afferent arteriolar tone during diabetes mellitus and that this phenomenon involves posttranslational modulation of channel function.
Authors:
Carmen M Troncoso Brindeiro; Pascale H Lane; Pamela K Carmines
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-17
Journal Detail:
Title:  Hypertension     Volume:  59     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-04-17     Revised Date:  2012-04-30    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  657-64     Citation Subset:  IM    
Affiliation:
Department of Cellular and Integrative Physiology, University of Nebraska College of Medicine, Omaha, NE, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology
Arterioles / drug effects,  metabolism*,  physiopathology
Blotting, Western
Cyclic N-Oxides / pharmacology*
Diabetes Mellitus, Experimental / drug therapy,  metabolism*
Gene Expression Regulation / drug effects
Kidney Cortex / blood supply*
Male
Muscle, Smooth, Vascular / drug effects,  metabolism
Oxidative Stress
Potassium Channels, Inwardly Rectifying / drug effects,  genetics,  metabolism*
RNA / genetics
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Spin Labels
Grant Support
ID/Acronym/Agency:
DK071152/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Cyclic N-Oxides; 0/Potassium Channels, Inwardly Rectifying; 0/Spin Labels; 2226-96-2/tempol; 63231-63-0/RNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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